Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Biology

Background:

• Synaptic integrity relies on a continuous supply of newly synthesized proteins.
• Proteins have finite lifetimes and require constant replenishment for neuronal function.
• Understanding protein supply disruptions is crucial for identifying neuronal failure points.

Purpose of the Study:

• To investigate neuronal and synaptic functions sensitive to protein synthesis suppression.
• To identify proteins lost early during compromised protein supply.
• To uncover potential failure points in neuronal homeostasis.

Main Methods:

• Acute suppression of protein synthesis in neuronal models.
• Assessment of spontaneous network activity, mitochondrial function, and synaptic stability.
• Proteomic analysis to identify early-lost proteins.

Main Results:

• Protein synthesis suppression rapidly reduced network activity and mitochondrial function within hours.
• Destabilization and loss of postsynaptic specializations occurred early.
• Proteomic analysis revealed early loss of proteins regulating synapse stability, bioenergetics, and Alzheimer's disease-related pathways.

Conclusions:

• Neuronal excitability, energy supply, and synaptic stability are early failure points when protein synthesis is compromised.
• Early-identified proteins suggest links between protein supply, synaptic health, and neurodegenerative diseases like Alzheimer's.
• These findings highlight the critical role of continuous protein synthesis in maintaining neuronal function and integrity.